Guo Yan-hong, Chen Feng-ying, Wang Gui-song, Chen Li, Gao Wei
Department of Cardiology, Peking University Third Hospital and Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100191, China.
Chin Med J (Engl). 2008 Nov 20;121(22):2265-71.
While hyperhomocysteinemia is associated with an increased risk of cardiovascular diseases, the effect of hyperhomocysteinemia on the vascular adventitia and vessel remodeling has not been clearly demonstrated. We investigated the effect of the hyperhomocysteinemia on adventitial hyperplasia and vascular remodeling following balloon injury in rats and the underlying mechanisms.
Rats were fed with diet containing methionine for 4 weeks to increase plasma homocysteine before balloon injury. Vascular geometrical changes were assessed at different time points following balloon injury. The collagen deposition was determined by picrosirius red staining and immunohistochemical staining.
When compared with normal diet group, moderate hyperhomocysteinemia in methionine diet group significantly exacerbated adventitial hyperplasia at day 7 and collagen deposition mainly in the adventitia at day 28 following balloon injury. The increased plasma homocysteine level significantly increased collagen deposition in the adventitia. There was a negative correlation (r = -0.698; P < 0.01) between the luminal area and the collagen content in the adventitia on day 28 following balloon injury. In cultured adventitial fibroblasts isolated from rat aorta, 100 micromol/L L-homocysteine (L-Hcy) significantly down-regulated matrix metalloproteinase-2 activity by 43% as determined by in vitro gelatin zymography (P < 0.05) and up-regulated the expression of collagen type I by 187% (P < 0.05) assessed by Western blotting.
Hyperhomocysteinemia exacerbated vascular constrictive remodeling by accelerated neointima formation and collagen accumulation in the adventitia. Increased collagen deposition may be the underlying mechanism.
虽然高同型半胱氨酸血症与心血管疾病风险增加相关，但高同型半胱氨酸血症对血管外膜和血管重塑的影响尚未得到明确证实。我们研究了高同型半胱氨酸血症对大鼠球囊损伤后外膜增生和血管重塑的影响及其潜在机制。
在球囊损伤前，给大鼠喂食含蛋氨酸的饮食4周以增加血浆同型半胱氨酸水平。在球囊损伤后的不同时间点评估血管几何形状变化。通过天狼星红染色和免疫组织化学染色测定胶原沉积。
与正常饮食组相比，蛋氨酸饮食组的中度高同型半胱氨酸血症在球囊损伤后第7天显著加剧了外膜增生，并在第28天主要在外膜增加了胶原沉积。血浆同型半胱氨酸水平升高显著增加了外膜中的胶原沉积。在球囊损伤后第28天，管腔面积与外膜胶原含量之间存在负相关（r = -0.698；P < 0.01）。在从大鼠主动脉分离的培养外膜成纤维细胞中，通过体外明胶酶谱法测定，100 μmol/L L-同型半胱氨酸（L-Hcy）显著下调基质金属蛋白酶-2活性43%（P < 0.05），并通过蛋白质印迹法评估上调I型胶原表达187%（P < 0.05）。
高同型半胱氨酸血症通过加速新生内膜形成和外膜胶原积累加剧血管收缩性重塑。胶原沉积增加可能是其潜在机制。
